This paper focuses on the study of an innovative manifold microchannel design for air-side heat transfer enhancement that uses additive manufacturing (AM) technology. A numerical-based multi-objective optimization was performed to maximize the coefficient of performance and gravimetric heat transfer density () of air–water heat exchanger designs that incorporate either manifold-microchannel or conventional surfaces for air-side heat transfer enhancement. Performance comparisons between the manifold-microchannel and conventional heat exchangers studied under the current work show that the design based on the manifold-microchannel in conjunction with additive manufacturing promises to push the performance substantially beyond that of conventional technologies. Different scenarios based on manufacturing constraints were considered to study the effect of such constraints on the heat exchanger performance. The results clearly demonstrate that the AM-enabled complex design of the fins and manifolds can significantly improve the overall performance, based on the criteria described in this paper. Based on the current manufacturing limit, up to nearly 60% increase in gravimetric heat transfer density is possible for the manifold-microchannel heat exchanger compared to a wavy-fin heat exchanger. If the manufacturing limit (fin thickness and manifold width) can be reduced even further, an even larger improvement is possible.